Drake Christopher R, Evans Michael J, VanBrocklin Henry F
Sofie Co., Culver City, CA, USA.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Methods Mol Biol. 2019;2033:191-205. doi: 10.1007/978-1-4939-9654-4_13.
There has been significant and rapid growth in the development of amino acid-based molecular imaging agents (e.g., peptides, proteins, and antibody constructs) largely due to facile library preparation and high throughput screening. Positron-emitting fluorine-18 (half-life = 109.7 min) has a unique set of properties that match well with the pharmacokinetics of smaller sized constructs. Several indirect fluorine-18 labeling approaches have been developed yet only a few have advanced to human trials. Enzymatically catalyzed radiofluorination utilizing lipoic acid ligase shows promise as a mild site-specific method for coupling fluorine-18-labeled carboxylate substrates with biomolecules. Methods for preparation of two [F]fluorocarboxylates and their ligation to a specific peptide sequence (LAP peptide) are presented herein.
基于氨基酸的分子成像剂（如肽、蛋白质和抗体构建体）的开发取得了显著且快速的进展，这主要归功于简便的文库制备和高通量筛选。发射正电子的氟 - 18（半衰期 = 109.7分钟）具有一组独特的性质，与较小尺寸构建体的药代动力学非常匹配。已经开发了几种间接氟 - 18标记方法，但只有少数进入了人体试验阶段。利用硫辛酸连接酶进行酶催化放射性氟化显示出有望成为一种温和的位点特异性方法，用于将氟 - 18标记的羧酸盐底物与生物分子偶联。本文介绍了两种[F]氟羧酸盐的制备方法及其与特定肽序列（LAP肽）的连接。
